This is a competing project renewal focusing on clinical depressive and anxiety disorders in children. These disorders are frequent, chronic, recurrent, and associated with significant morbidity, functional impairment, and mortality. Three inter-related domains which are crucial furthering our understanding of this disorder will be studied: (1) the longitudinal episodic and chronic course of these disorders and their interrelationship within the developing child. (2) the role of early adversity and stressful life events in initiation and maintenance of depressive and anxiety disorders in this population and the potentialameliorative role of social supports. (3) The developing biological organism with specific measurable systems which appear strongly related to these disorders in children including: (a) frontal brain circuitry involved in withdrawal-related negative affect, (b) the hypothalamic-pituitary-adrenal system, (c) sleep, (d) serotonergic systems, and (e) growth hormone control. A new sample of children with clinical anxiety disorders, children with clinical depression disorders and normal control children will be studied in three projects examining course, life events, and psychobiology. Those children along with depressed, "high risk" and normal children ascertained and studied psychobiologically in years 01-10 will be followed longitudinally with measures of life events and course. A separate "high risk"cohort of children followed prospectively since age 1 will be studied with sleep and cortisol measures in the home in order to export our work in the lab to a larger, more diverse population and to better understand the effects of very early development. Finally, a juvenile primate model will be used to elucidate the role of anxiety and stress in GH dysregulation and to identify the underlying neural circuity controlling this well replicated finding in these disorders in humans throughout the life span. This program project may lead to better prediction of risk and course and better prevention, treatment, and prophylaxis strategies for depressive and anxiety disorders in children.